Highly active antiretroviral therapy (HAART) has led to better health and survival rates among people with HIV/AIDS. The purpose of this study was to measure the effect of trained partner supervision when taking medication versus self-administered therapy in HIV infected participants. These participants have had their first virologic failure on a non-nucleoside reverse transcriptase inhibitor (NNRTI)-based HAART regimen and were starting a protease inhibitor (PI)-based HAART regimen at study entry.

Confirmed Virologic Failure at or Prior to Week 48 [ Time Frame: At or prior to Week 48 ] [ Designated as safety issue: Yes ]

Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) <1 log10 copies/mL below the baseline level and >400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) >400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤50 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 48 was reported.

Secondary Outcome Measures:

Confirmed Virologic Failure at or Prior to Week 24 [ Time Frame: At or prior to Week 24 ] [ Designated as safety issue: Yes ]

Confirmed virologic failure was defined as two successive HIV-1 RNA measurements at least 24 hours apart that were either:1) <1 log10 copies/mL below the baseline level and >400 copies/mL at the week 12 HIV-1 RNA evaluation (obtained at least 11 weeks after the date of the randomization) 2) >400 copies/mL at or after the week 24 HIV-1 RNA evaluation (obtained at least 23 weeks after the date of randomization). 3) subjects who discontinued the study follow-up for any reason other than study completion, including death, and who did so ≤30 weeks after randomization was considered to be a virologic failure. Number of participants experiencing or not experiencing virologic failure at or prior to week 24 was reported.

Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Modified directly observed therapy (mDOT) for the first 24 weeks and self-administration for the remaining 28 weeks.

Drug: Lopinavir/ritonavir

Two tablets (200-mg lopinavir and 50 mg ritonavir in each tablet), taken orally twice daily

Other Names:

LPV/RTV

LPV/r

Kaletra

Drug: Emtricitabine/Tenofovir disoproxil fumarate

200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily

Other Names:

FTC/TDF

Truvada

Drug: Tenofovir disoproxil fumarate

300-mg tablet taken orally once daily

Other Names:

TDF

Viread

Drug: Zidovudine

300-mg tablet taken orally twice daily

Other Names:

ZDV

Retrovir

Drug: Emtricitabine

200-mg tablet taken orally once daily

Other Names:

FTC

Emtriva

Active Comparator: non-mDOT arm

Oral FTC/TDF+LPV/rtv or TDF+ZDV+LPV/rtv for 52 weeks. Self-administration of the study treatment (non-mDOT) for 52 weeks.

Drug: Lopinavir/ritonavir

Two tablets (200-mg lopinavir and 50 mg ritonavir in each tablet), taken orally twice daily

Other Names:

LPV/RTV

LPV/r

Kaletra

Drug: Emtricitabine/Tenofovir disoproxil fumarate

200-mg emtricitabine and 300 mg tenofovir disoproxil fumarate in each tablet, taken orally once daily

Other Names:

FTC/TDF

Truvada

Drug: Tenofovir disoproxil fumarate

300-mg tablet taken orally once daily

Other Names:

TDF

Viread

Drug: Zidovudine

300-mg tablet taken orally twice daily

Other Names:

ZDV

Retrovir

Drug: Emtricitabine

200-mg tablet taken orally once daily

Other Names:

FTC

Emtriva

Detailed Description:

Poor adherence to HAART is usually associated with resistant virus. Poor adherence to HAART can have serious consequences, including limited treatment options for HIV infected individuals if they become infected with resistant HIV. The purpose of this study was to examine the effectiveness of modified directly observed therapy (mDOT) and compare it with the effectiveness of self-administered therapy (non-mDOT) in HIV infected individuals with first virologic failure on an NNRTI-based HAART regimen who were starting a PI-based HAART regimen at study entry.

mDOT was defined in this study as the daily observation of lopinavir/ritonavir (LPV/r) being taken on a regular basis. Observation consisted of an mDOT partner being present at the time the study participant took the observed dose. Half of the participants in this study were required to choose an mDOT partner to supervise adherence for the first 24 weeks of the study. Each mDOT partner completed the study-administered mDOT training program and was required to record all observed doses in an mDOT diary log. All participants and partners received health education through the study. Adherence was measured using Medication Event Monitoring System (MEMS) caps and self-report questionnaires.

This study lasted 52 weeks. Per protocol, participants were to be stratified according to their screening viral load and the proposed study treatment. The study treatment each participant received was based on their treatment history. At entry, participants were to start one of the two PI-based HAART regimens, either FTC/Tenofovir Disoproxil Fumarate (TDF) 200/300 mg once daily (QD) and Lopinavir/Ritonavir (LPV/RTV) 400/100 mg twice a day (BID) or TDF 300 mg QD and zidovudine (ZDV) 300 mg BID and LPV/RTV 400/100 mg BID. mDOT was used for the first 24 weeks of the study, followed by self-administration of study medications from week 25 to week 52. ZDV was not provided by the study. All enrolled participants except one who did not start study regimen initiated FTC/TDF and LPV/rtv after randomization. No participants started ZDV containing regimen on study. Thus, participants in this study were stratified by screening HIV-1 RNA only.

There were eight visits during the study. Medical and medication history, blood collection, and clinical assessment were required at all visits. A quality of life questionnaire and an adherence tools assessment were collected at most visits. For the mDOT arm, medication diary logs and mDOT partner monitoring were reviewed at most visits. An mDOT exit questionnaire and exit interview were required at the end of the study.

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria for Participants:

HIV infected

Have experienced or currently experiencing first baseline virologic failure on first NNRTI-based HAART regimen with no history of virologic failure on another regimen OR discontinued first NNRTI-based HAART regimen without the recommendations of clinicians and currently experiencing virologic failure with no history of virologic failure on another regimen. More information on this criterion can be found in the protocol.

Confirmed virologic failure within 45 days of study entry

Receiving one of the following NNRTI-based regimens for at least 16 weeks prior to study entry: ZDV+3TC+NVP, ZDV+3TC+EFV, d4T+3TC+NVP or d4T+3TC+EFV

Able to identify a close friend, relative, or spouse who is willing to serve as a partner

Intend to stay in current geographical area of residence for the duration of the study

Agree to use LPV/rtv with MEMS caps and take the tablets out of the container only at dosing

Willing to use acceptable forms of contraception

Ability and willingness of participant or legal guardian/representative to give written informed consent.

Use of rifampin or rifabutin within 45 days of study entry or plan use of rifampin or rifabutin

Requirement for taking any medications that are prohibited by this study. More information on this criterion can be found in the protocol.

Known allergy to the study medications or their formulations

Current drug or alcohol use that, in the opinion of the investigator, would interfere with the study

Acute illness requiring hospitalization within 14 days of study entry

Active tuberculosis (TB) infection

Currently incarcerated

Participation as a partner in this study

Participation with no access to telephones

Abnormal laboratory values

Pregnant, breastfeeding, or intend to become pregnant

Exclusion Criteria for Partners:

A participant in this study

Participation as a partner to any other participant

No access to telephones

Currently incarcerated

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00608569